Manufacture of aldehydes and ketones



United States Patent 7 3,157,703 MANUFACTURE OF ALDEHYDES AND KETONESVolirer Franzen, Heidelherg-Wieblingen, Germany,

assignor to Cariisle Chemical Works, Inc, Reading, ()hio, a corporationof Ohio No Drawing. Filed Mar. 28, 1962, Ser. No. 183,020 Ciaimspriority, application Germany Apr. 5, 1961 I 11 Claims. (Cl. 260-586)The present invention relates to a process for the preparation ofaldehydes and ketones.

Various procedures have been proposed in the past for forming aldehydesand ltetones from alkylating agents such as alkyl halides, alkylchlorosulfonic acid esters, alkyl p-toluene sulfonic acid esters(tosylates), alkyl sulfuric acid esters and alkyl sulfites. However,none of these methods permitted the alkylating agent to be directlyconverted to the corresponding aldehyde or ketone.

Instead the previous procedures required at least two steps. In additionthe yields by such prior art procedures in many cases gave poor yieldsof the desired products.

Accordingly it is an object of the present invention to devise a newprocedure for preparing aldehydes and ketones.

Another object is to develop a one step procedure for preparingaldehydes and ketones from alkylating agents.

A further object is to prepare aldehydes and ketones in improved yields.

Yet another object is to prepare aldehydes and ketones from readilyavailable materials such as alkyl halides and other esters.

Still further objects and the entire scope of applicability of thepresent invention will become apparent from the detailed descriptiongiven hereinafter; it should be understood, however, that the detaileddescription and specific examples, while indicating preferredembodiments of the invention, are given by way of illustration only,since various changes and modifications Within the spirit and scope ofthe invention will become apparent to those skilled in the art from thisdetailed description.

It has now been found that these objects can be attained by reactingtrimethylamine oxide with alkylating agents such as alkyl halides, alkylesters of chlorosulfonic acid, alkyl esters of p-toluene sulfonic acid,alkyl esters of benzene sulfonic acid, alkyl esters of sulfuric acid,alkyl esters of sulfuorous acid and also the corresponding cycloalkyl,alkenyl and aromatic esters of these acids. The reaction goes smoothlyin a one step procedure according to the following equation.

In the formula R is H, alkyl or aryl R is alkyl, alkenyl,

aryl, aralkenyl, nitroaryl or haloaryl or R and R are joined togetherwith the C to form a cycloalkyl or cycloalkenyl group. X is halogen, RSO O where R is aryl or alkyl, OSO Cl,

os" oRr 1 where R is alkyl or O S R3 where R is alkyl.

When X is halogen preferably it has an atomic weight between 35 and 127.

As examples of suitable alkylating agents there can be used ethyliodide, ethyl bromide, propyl chloride, propyl bromide, propyl iodide,isopropyl bromide, n-butyl bromide, isobutylbromide, sec butyl bro}mide, n-butyl chloride, n-butyl iodide, n-hexyl iodide, n-hexyl bromide,n-arnyl chloride, neopentyl bromide, n-octyl iodide, n-octyl chloride,n-octyl bromide, isoamyl bromide, n-dodecyl bromide, cetyl bromide,cetyl chlorosulfonate, cyclooctyl chlorosulionate, sec amyl but can berecovered quite readily after the completion e.g. a mineral acid afterit is cooled. Such acids include of the reaction. The process canbeapplied generally to prepare aliphatic, aromatic, branched chain,straight chain, cycloaliphatic, saturated and unsaturated alde hydes andketones. 1

In carrying out the procedure, the alkylating agent, e.g. the alkylhalide or the chlorosulfonic or tosyl ester is reacted in equal molaramounts or with an excess of anhydrous trimethylarnine oxide. The molarratio of the alkylating agent to the trimethylamine oxide is preferablybetween 1:1 and 1:4. It is desirable to run the reaction in an organicsolvent in which the trimethylamine oxide is soluble, e.g. inchloroform. The reaction can also be carried out in other solvent suchas methylene chloride, dioxane, tetrahydrofuran, benzene, toluene,carbon tetrachloride xylene and dimethylformamide.

The reaction time is generally not longer than 20-30 minutes. In somecases it is even shorter. In many cases the resulting heat of reactionis sufiicient; in other cases, particularly with long chain halides andtosylates, additional heating is necessary to complete the reaction.

The exact reaction conditions naturally vary from case to case. Too longa heating period is'to be avoided since the aldehydes formed can reactfurther occasionally according to the aldol condensation in basicmedium. It the heating period is too long and the excess oftrimethylamine oxide is much too large, further oxidation occurs.

'However, both of these troublesome side reactions named above proceedconsiderably slower than the desired aldehyde or ketone formation sothat an additional margin remains for the latter reaction and, ifnecessary, conditions of time and temperature, under which the carbonylcompound can be isolated without difficulty, can always be found bypreliminary experiments.

To isolate the reaction product, the reaction solution, e.g. achloroform solution, is shaken with a strong acid,

hydrochloric acid, sulfuric acid and phosphoric acid. Then the aqueouslayer is separated and the chloroform solution is washed with aqueoussodium bicarbonate or potassium bicarbonate solution. Then afterseparating Patented Nov. 3?, 19%4 the aqueous layer and drying, thechloroform solution is distilled. Also, after first cooling the reactionsolution, the ammonium salt formed in the reaction can be precipitatedby the addition of ether. If the aldehyde or the lzetone is stable, itcan be recovered as the residue simply by distilling off the solventafter the removal of the ammonium salt.

Anhydrous trimethylamine oxide can be prepared from its hydrate in anyconvenient fashion, see Fieser et a1. Organic Chemistry pages 239-240but is preferably prepared by dehydration with dimethyl formamide, e.g.according to the following procedure:

40 g. trimethylamine oxide hydrate were dissolved with heating in 250ml. of dry dimethyl formamide. It was heated further on an oil bathuntil the distillate had reached the boiling point of the dimethylformamide. Then the bath was allowed to cool to about 65 C. and theresidual solvent was distilled in the vacuum (waterjet) pump while theoil bath was reheated slowly to 120. Anhydrous trimethyl'amine oxideremained behind, M.P. 210 C. Yield: 22 g.

Unless otherwise indicated all parts and percentages are by weight.

The yields given in the following examples are of the pure, distilledfinal products.

EXAMPLE 1 Preparation of Hexanal-I 0.2 mol of n-hexyl iodide was slowlyadded dropwise under agitation to a solution of 0.2 mol of anhydroustrimethylamine oxide in 55 ml. of chloroform. At the beginning it washeated on the water bath to 50-60 C. When about half of the hexyl iodidewas added, the alkylation reaction started whereby the chloroform cameto the boiling point. The Water bath was removed and the remainder ofthe hexyl iodide was added dropwise. Subsequently the mixture boiledunder reflux for 30 minutes. After cooling, 55 ml. of 2 N hydrochloricacid were added, mixed thoroughly, and the layers separated. Thechloroform solution was washed with aqueous sodium bicarbonate solution,dried, and distilled.

Boiling Point: 38 C. at min. Yield: 9.7 g.

Similar yields of hexanal-l were obtained by replacing the hexyl iodideby 0.2 mol of n-hexyl bromide in this example.

EXAMPLE 2 Preparation of Octanal-l 0.2 mol of n-octyl iodide was addedslowly under agitation to a solution of 0.2 mol of trimethylamine oxidein 55 ml. of chloroform. The solution was heated slightly at thebeginning until the reaction began. After all of the octyl iodide wasadded dropwise, the mixture was boiled under reflux for 30 minutes. Itwas cooled and 55 ml. of 2N hydrochloric acid were added. The solutionwas mixed thoroughly, then the layers were separated. The chloroformsolution was washed with aqueous potassium bicarbonate solution anddried. Then it was distilled.

Boiling Point: 77 C. at 25 mm. Yield: 12.5 g.

EXAMPLE 3 Reaction of Octyl Tosylate With T rimethylamine Oxide Usingthe same procedure as in Example 2, 0.2 mol of n-octyl tosylate wasreacted with 0.4 mol of trimethylamine oxide. The heating period wasminutes. n- Octanal-l was obtained in a 55% theory yield.

EXAMPLE 4 Reaction of the Octyl Ester of Chlorosulfonic Acid With Trimethylamine Oxide Under cooling and good agitation 0.15 mol of theoctyl ester of chlorosulfonic acid was added dropwise to a solution of0.53 mol of trimethylamine oxide in 150 ml. of chloroform. The reactionbegan immediately.

After the addition was completed, the chloroform solution was washedthoroughly with 2 N hydrochloric acid and then with sodium bicarbonatesolution. It was dried and distilled.

Boiling Point of obtained octanol: B.P. 65 C. Yield: 10 g.

EXAMPLE 5 Preparation of Isovaleraldehyde Using the same procedure as inExample 2.

0.027 mol of isoamyl bromide and 0.53 mol trimethylamine oxide werereacted to give isovaleraldehyde. B.P.750

EXAMPLE 6 Reaction of Di-n-Amyl Sulfate With T imethylamine Oxide Withcooling 0.15 mol of di-n-amyl sulfate was added dropwise to a solutionof 0.4 mol of trimethylamine oxide in 200 ml. of methylene chloride. Aperceptible reaction took place. After the addition was completed, themixture was heated 10 minutes up to boiling. The ammonium salt formedwas removed by washing with 2 N sulfuric acid and the organic solutionwas distilled to remove solvents. There was recovered as a residuenvaleraldehyde in a yield of 7.4 g.

EXAMPLE 7 Preparation of Dodecanal-I 0.2 mol of n-dodecyl bromide wasadded dropwise with slight heating and agitation to a solution of 0.4mol of trimethylamine oxide in ml. of chloroform. After the addition thesolution was boiled under reflux for 20 minutes. The solution was cooledand treated with double its volume of ether. Thereby the ammonium saltformed precipitated and was separated. The etherchloroform solution waswashed thoroughly with 2 N hydrochloric acid and then aqueous sodiumbicarbonate solution and dried. After removal of the solvents, theresidue was fractionated to obtain dodecanal-l.

Boiling Point: B.P. 144-145. Yield 21 g.

EXAMPLE 8 Preparation of Palmiticaldehyde 0.2 mol of cetyl iodide wasslowly added dropwise to a solution of 0.5 mol of trimethylamine oxidein 150 ml. of chloroform. During the dropwise addition, the chloroformsolution washeated slightly. The solution was boiled under reflux for 30minutes. After cooling, the chloroform solution was treated with 400 ml.ether, whereby all of the ammonium salt formed was precipitated. Theprecipitate was separated, the ether-chloroform solution Washed with 2 Nhydrochloric acid and aqueous sodium bicarbonate solution and dried.

The solvent was distilled under nitrogen. The residue crystallized onstanding to give palmitic aldehyde, melting point 35 C. Yield 24 g.

Using the same procedure as Example 8 but replacing the cetyl iodidewith 0.2 mol of the cetyl alcohol ester of chlorosulfonic acid anequally good yield of palinitic aldehyde was obtained. Similarly using0.2 mol of cetyl bromide in place of cetyl iodide gave a good field ofpalmitic aldehyde.

EXAMPLE 9 Preparation of Stearic Aldehyde Using the method of Example 8,0.2 mol of stearyl chlorosulfonate was reacted with 0.5 mol oftrimethylamine oxide in 150 ml. of chloroform to give stearicaldehyde,melting point 38 C. in a yield of 22 g.

EXAMPLE 10 Preparation of Benzaldehyde 0.2 mol of anhydroustrimethylamine oxide was dissolved in 55 ml. of chloroform and chargedinto a threeneck flask equipped with an agitator, dropping funnel, andreflux condenser. With cooling, 0.1 mol of benzyl chloride was addeddropwise. Then the mixture was heated slowly to boiling and boiled underreflux for 50 minutes. After cooling, the solution was treated with anequal volume of 2 N hydrochloric acid, the layers are separated, and thechloroform solution was washed with aqueous sodium bicarbonate solution.The chloroform solution was dried and distilled.

Yield of benzaldehyde: 46% of theory. Similar Yields of benzaldehydewere obtained by replacing the benzyl chloride by 0.1 mol of benzylbromide in Example 10.

EXAMPLE 11 Preparation of Benzaldehyde The procedure of Example wasmodified by replacing the benzyl chloride with 0.2 mol benzyl tosylateand by utilizing 0.4 mol of trimethylamine oxide in 110 ml. ofchloroform. The benzaldehyde was obtained in a yield of 45% of theory.

EXAMPLE 12 Preparation of p-Nitrobenzaldehyde 0.2 mol of anhydroustrimethylamine oxide was dissolved in 60 ml. of chloroform and chargedinto a threeneck flask equipped with agitator, reflux condenser, anddropping funnel. With cooling, 0.15 mol p-nitrobenzyl chloride dissolvedin 50 ml. of chloroform was added dropwise. The reaction solution becamewarm. After the addition was completed, the mixture was allowed to standanother 10 minutes at room temperature, then shaken thoroughly with 2 Nsulfuric acid, the aqueous layer separated, and the chloroform layerdried and evaporated under vacuum. The p-nitrobenzaldehyde remainedbehind, as a residue having a melting point of 107 C. The yield Was 12.1g.

EXAMPLE 13 Preparation 0 p-Tolylaldehyde 0.2 mol of anhydroustrimethylamine oxide was dissolved in 60 ml. of chloroform and withagitation was treated with 0.15 mol of p-methylbenzyl chloride. Thehalide was slowly added dropwise. Subsequently the mixture was boiledunder reflux for minutes. The

chloroform solution was washed thoroughly with 2 N sulfuric acid anddried. After removing the solvents, the p-tolylaldehyde remained behind.

Boiling Point 204 C. Yield 9.2 grams.

EXAMPLE 14 Preparation of Cinnamaldehyde 0.2 mol of anhydroustrimethylamine oxide was dissolved in 60 ml. of chloroform. Withagitation and cooling, a solution of 0.1 mol of cinnamyl chloride in 50ml. of chloroform was added dropwise. The reaction solution became warm.After the addition was completed, the mixture was allowed to stand atroom temperature for 20 minutes. Then the chloroform solution was Washedwith 2 N sulfuric acid and dried. After the removal of the solvent, thecinnamaldehyde remained behind, B.P. 158 C. Yield 6.4 g.

EXAMPLE 15 Preparation of Cyclopentanone 0.2 mol of cyclopentyl bromidewas added dropwise to a solution of 0.4 mol of trimethylamine oxide in110 ml. of chloroform. At the beginning the mixture was heated slightly.After the addition of the cyclopentyl bromide was completed the mixturewas heated under reflux for 1% hours. Theammonium salt formed wasremoved by washing with 2 N hydrochloric acid. After drying, thechloroform was distilled ofi. The cyclopentanone residue had a B3 130 C.and was obtained in a yield of 10 g.

EXAMPLE 16 Preparation of Cyclooctanone 0.2 mol of anhydroustrimethylamine oxide was dissolved in 60 ml. of chloroform. Withagitation 0.1 mol of cyclooctyl bromide was added dropwise. Then themixture was boiled under reflux for 30 minutes. The ammonium salt formedwas removed by washing with 2N sulfuric acid. The solvent was removed bydistillation. I

The cyclooctanone remained behind.

Boiling point 197 C. Yield 8.1 g.

EXAMPLE 17 Preparation of Cyclooctanone 0.2 mol of anhydroustrimethylamine oxide was dissolved in ml. of methylene chloride. Withagitation 0.1 mol of the cyclooctyl ester of chlorosulfonic acid wasadded dropwise then the mixture was boiled under reflux for 30 minutes.The mixture was allowed to cool and the ammonium salt formed was thenprecipitated by the addition of ether and removed. The solvent Was thendistilled off to leave a residue of the desired cyclooctanone, 13.1.197.

EXAMPLE 18 Preparation of Diethyl Ketone Utilizing the procedure ofExample 16 0.15 mol of the n-pentan-ol-3 ester of p-toluene sulfonicacid was reacted with 0.2 mol of trimethylamine oxide to produce 7.2grams of pentanone-3 (diethyl ketone) I claim:

1. A process of preparing a carbonyl compound of the group consisting ofaldehydes and ketones comprising reacting trimethylamine oxide with analkylating agent having a formula selected from the group consisting ofOSO Cl l -o s o R4 where R; is alkyl, and

o s 0 R6 where R is alkyl.

2. A process according to claim 1 wherein the molar ratio oftrimethylamine to the alkylating agent lies between the limits 1: 1 and4: 1. g

3. A process according to claim 1 wherein the reaction is carried out inan organic solvent selected from the group consisting of polychlorinatedaliphatic hydrocarbons, dioxane, aromatic hydrocarbons, tetrahydrofuraneand dimethyl formamide.

4. A process according to claim 3 wherein the reaction is carried outwith heating at a temperature up to the boiling point of the solvent.

5. A process according to claim 1 wherein the reaction is carried out inan organic solvent, and the reaction solution is acidified with aqueousmineral acid, separated from the acid, Washed with alkaline bicarbonatesolution and then the carbonyl compound is recovered by removing thesolvent by distillation.

6. A process according to claim 1 wherein the reaction is carried out inan organic solvent, the ammonium salt formed is precipitated from thereaction solution by the addition of ether and the precipitate isseparated from the solution.

7. A process of preparing an aldehyde comprising reacting anhydroustrimethylamine oxide with a primary alkyl halide having at least twocarbon atoms, the halogen of said halide having an atomic weight ofbetween 35 and 127.

8. A process of preparing an aldehyde comprising reacting anhydroustrimethylamine oxide with a primary dialkyl sulfate, said alkyl groupshaving at least two carbon atoms.

9. A process of preparing an aldehyde comprising reacting anhydroustrimethylarnine oxide with an aralkenyl halide having a single aromaticring, the halogen of said halide having an atomic weight between 35 and127.

10. A process of preparing a cyclic ketone comprising reacting anhydroustrimethylar'nine oxide with a cycloalkyl halide, the halogen of saidhalide having an atomic weight between 35 and 127.

11. A process of preparing a dialkyl ketone comprising reactinganhydrous trimethyiamine oxide with a secondary alkyl halide having atleast three carbon atoms, the halogen of said halide having an atomicweight between 35 and 127.

References Cited in the file of this patent UNITED STATES PATENTS2,888,488 Nace May 26, 1959

1. A PROCESS OF PREPARING A CARBONYL COMPOUND OF THE GROUP CONSISTING OFALDEHYDES AND KETONES COMPRISING REACTING TRIMETHYLAMINE OXIDE WITH ANALKYLATING AGENT HAVING A FORMULA SELECTED FROM THE GROUP CONSISTING OF